Regulatory RNAs in Heart Failure Gomes, Clarissa Pedrosa Costa; Schroen, Blanche; Kuster, Gabriela M ...
Circulation (New York, N.Y.),
2020-January-28, Letnik:
141, Številka:
4
Journal Article
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Cardiovascular disease is an enormous socioeconomic burden worldwide and remains a leading cause of mortality and disability despite significant efforts to improve treatments and personalize ...healthcare. Heart failure is the main manifestation of cardiovascular disease and has reached epidemic proportions. Heart failure follows a loss of cardiac homeostasis, which relies on a tight regulation of gene expression. This regulation is under the control of multiple types of RNA molecules, some encoding proteins (the so-called messenger RNAs) and others lacking protein-coding potential, named noncoding RNAs. In this review article, we aim to revisit the notion of regulatory RNA, which has been thus far mainly confined to noncoding RNA. Regulatory RNA, which we propose to abbreviate as regRNA, can include both protein-coding RNAs and noncoding RNAs, as long as they contribute, directly or indirectly, to the regulation of gene expression. We will address the regulation and functional role of messenger RNAs, microRNAs, long noncoding RNAs, and circular RNAs (ie, regRNAs) in heart failure. We will debate the utility of regRNAs to diagnose, prognosticate, and treat heart failure, and we will provide directions for future work.
Inflammatory biomarkers are associated with severity of coronavirus disease 2019 (COVID-19). However, direct comparisons of their utility in COVID-19 versus other respiratory infections are largely ...missing.
We aimed to investigate the prognostic utility of various inflammatory biomarkers in COVID-19 compared to patients with other respiratory infections.
Patients presenting to the emergency department with symptoms suggestive of COVID-19 were prospectively enrolled. Levels of Interleukin-6 (IL-6), c-reactive protein (CRP), procalcitonin, ferritin, and leukocytes were compared between COVID-19, other viral respiratory infections, and bacterial pneumonia. Primary outcome was the need for hospitalisation, secondary outcome was the composite of intensive care unit (ICU) admission or death at 30 days.
Among 514 patients with confirmed respiratory infections, 191 (37%) were diagnosed with COVID-19, 227 (44%) with another viral respiratory infection (viral controls), and 96 (19%) with bacterial pneumonia (bacterial controls). All inflammatory biomarkers differed significantly between diagnoses and were numerically higher in hospitalized patients, regardless of diagnoses. Discriminative accuracy for hospitalisation was highest for IL-6 and CRP in all three diagnoses (in COVID-19, area under the curve (AUC) for IL-6 0.899 95%CI 0.850-0.948; AUC for CRP 0.922 95%CI 0.879-0.964). Similarly, IL-6 and CRP ranged among the strongest predictors for ICU admission or death at 30 days in COVID-19 (AUC for IL-6 0.794 95%CI 0.694-0.894; AUC for CRP 0.807 95%CI 0.721-0.893) and both controls. Predictive values of inflammatory biomarkers were generally higher in COVID-19 than in controls.
In patients with COVID-19 and other respiratory infections, inflammatory biomarkers harbour strong prognostic information, particularly IL-6 and CRP. Their routine use may support early management decisions.
We review observational, experimental, and model results on how plants respond to extreme climatic conditions induced by changing climatic variability. Distinguishing between impacts of changing mean ...climatic conditions and changing climatic variability on terrestrial ecosystems is generally underrated in current studies. The goals of our review are thus (1) to identify plant processes that are vulnerable to changes in the variability of climatic variables rather than to changes in their mean, and (2) to depict/evaluate available study designs to quantify responses of plants to changing climatic variability. We find that phenology is largely affected by changing mean climate but also that impacts of climatic variability are much less studied, although potentially damaging. We note that plant water relations seem to be very vulnerable to extremes driven by changes in temperature and precipitation and that heatwaves and flooding have stronger impacts on physiological processes than changing mean climate. Moreover, interacting phenological and physiological processes are likely to further complicate plant responses to changing climatic variability. Phenological and physiological processes and their interactions culminate in even more sophisticated responses to changing mean climate and climatic variability at the species and community level. Generally, observational studies are well suited to study plant responses to changing mean climate, but less suitable to gain a mechanistic understanding of plant responses to climatic variability. Experiments seem best suited to simulate extreme events. In models, temporal resolution and model structure are crucial to capture plant responses to changing climatic variability. We highlight that a combination of experimental, observational, and/or modeling studies have the potential to overcome important caveats of the respective individual approaches.
► Formulation of processes in reinforced concrete relevant for corrosion of steel. ► 3D finite element formulation of the processes relevant for corrosion of steel. ► Implementation of the ...formulation into a 3D finite element code. ► 3D finite element study for RC beam in the splash zone.
The paper deals with a 3D numerical model for transient analysis of processes after depassivation of reinforcement in concrete, which are relevant for calculation of corrosion rate. The aim of the study is to investigate the influence of the concrete quality, cracking and water saturation in concrete on the current density. The results show that the corrosion rate is higher in poor quality concrete than in good quality concrete. The model predicts that cracks do not influence corrosion rate for the case where the only influence of the crack is on the rate at which oxygen can reach the steel.
ACL-reconstruction aims to restore joint stability and prevent osteoarthritis; however, malfunction and osteoarthritis are often the sequelae. Our study asks whether ACL-reconstruction or ...conservative treatment lead to better long-term results. In this retrospective cohort study, 136 patients with isolated ACL-rupture who had been treated by bone-ligament-bone transplant or conservatively were identified. Twenty-seven of these were excluded because of a revision operation in the 11.1 years follow-up period, leaving 109 patients (60 reconstructions and 49 conservatively treated) for evaluation based on clinical, radiological and internationally accepted knee-scores (Tegner, IKDC, Kellgren and Lawrence). An individual cohort study is classified as EBM level 2b according to the Oxford Centre of EBM. We observed significantly better knee-stability (
P =
0.008) but more osteoarthritis (Grade II or higher) after ACL-reconstruction (42% vs. 25%). Physical activity levels were similar in both groups during the follow-up period (
P =
0.16). Eleven years after ACL-rupture the physical activity levels are similar for both groups. After ACL-reconstruction, stability is higher as is osteoarthritis, whereby the result is not necessarily perceived as better subjectively. Specifically, this retrospective study yielded a 24% incidence of oseoarthrits 11 years after conservative management of ACL-rupture in patients not needing secondary surgery. The risk of secondary meniscal tears is reduced after ACL reconstruction, which reduces the negative effects of OA after surgery. The ultimate objective would be to achieve a good subjective outcome by conservative treatment followed by a rehabilitation program designed to keep secondary meniscus tears at a low level.
Climate change is expected to increase temperature and decrease summer precipitation in Central Europe. Little is known about how warming and drought will affect phenological patterns of oaks, which ...are considered to possess excellent adaptability to these climatic changes. Here, we investigated bud burst and intra-annual shoot growth of Quercus robur, Q. petraea and Q. pubescens grown on two different forest soils and exposed to air warming and drought. Phenological development was assessed over the course of three growing seasons. Warming advanced bud burst by 1-3 days °C⁻¹ and led to an earlier start of intra-annual shoot growth. Despite this phenological shift, total time span of annual growth and shoot biomass were not affected. Drought changed the frequency and intensity of intra-annual shoot growth and advanced bud burst in the subsequent spring of a severe summer drought by 1-2 days. After re-wetting, shoot growth recovered within a few days, demonstrating the superior drought tolerance of this tree genus. Our findings show that phenological patterns of oaks are modified by warming and drought but also suggest that ontogenetic factors and/or limitations of water and nutrients counteract warming effects on the biomass and the entire span of annual shoot growth.
Besides noticeable progress in device therapy during the past decade, more recent advances in the management of chronic heart failure have led to exciting new pharmacological options. Among these, ...the combined angiotensin II receptor/neprilysin inhibitor (ARNI) valsartan/sacubitril has already proven highly effective in heart failure with reduced ejection fraction (HFrEF), and convincing data are available regarding the cardioprotective effects of sodium-glucose-co-transporter 2 (SGLT2) inhibitors. These two treatments have earned a class I and a class II recommendation, respectively, in the European Society of Cardiology guidelines for the diagnosis and treatment of heart failure. Whereas progress with respect to heart failure with preserved ejection fraction (HFpEF) is still slow, both ARNIs and SGLT2 inhibitors hold great promise for this condition as well, and large clinical trials are currently ongoing. In addition, new diagnostic algorithms have recently been developed to improve the diagnostic accuracy for HFpEF, which will ultimately aid the search for effective therapies in future clinical trials. In this review article, these most recent advances in the diagnosis and pharmacological management of HFrEF and HFpEF are highlighted, and set-backs as well as opportunities for future developments (e.g., tafamidis for the treatment of transthyretin amyloid cardiomyopathy) are discussed.
Global environmental changes affect not only the aboveground but also the belowground components of ecosystems. The effects of seasonal drought and air warming on the genus level richness of ...Collembola, and on the abundance and biomass of the community of Collembola and mites were studied in an acidic and a calcareous forest soil in a model oak-ecosystem experiment (the Querco experiment) at the Swiss Federal Research Institute WSL in Birmensdorf. The experiment included four climate treatments: control, drought with a 60% reduction in rainfall, air warming with a seasonal temperature increase of 1.4 °C, and air warming + drought. Soil water content was greatly reduced by drought. Soil surface temperature was slightly increased by both the air warming and the drought treatment. Soil mesofauna samples were taken at the end of the first experimental year. Drought was found to increase the abundance of the microarthropod fauna, but reduce the biomass of the community. The percentage of small mites (body length ≤ 0.20 mm) increased, but the percentage of large mites (body length >0.40 mm) decreased under drought. Air warming had only minor effects on the fauna. All climate treatments significantly reduced the richness of Collembola and the biomass of Collembola and mites in acidic soil, but not in calcareous soil. Drought appeared to have a negative impact on soil microarthropod fauna, but the effects of climate change on soil fauna may vary with the soil type.
The calculation of corrosion current density, during the process of electrochemical steel corrosion in concrete, requires modelling of the following physical and electrochemical processes: transport ...of capillary water, oxygen and chloride through the concrete cover, immobilization of chloride in the concrete, transport of OH
− ions through electrolyte in concrete pores and cathodic and anodic polarization. The paper deals with a 3D numerical model for transport of capillary water, oxygen and chloride through the concrete. The model is formulated in the framework of continuum mechanics following basic principles of irreversible thermodynamics. The mechanical part of the model is based on the hygro-thermo dependent microplane model of concrete. Damage and cracking phenomena are modelled within the concept of smeared cracks (weak discontinuity). The interaction between the non-mechanical processes (distribution of temperature, capillary water, oxygen and chloride) and mechanical properties of concrete (damage) is taken into account. The strong and weak formulations of the model and the implementation into a 3D finite element code are discussed. The formulation is restricted to the processes leading to depassivation of reinforcement. The application of the model is illustrated on a numerical example in which the transient 3D finite element analysis of RC slab is carried out to investigate the influence of damage of concrete on depassivation time of reinforcement. In the analysis, the undamaged and damaged parts of previously loaded RC slabs are exposed to the aggressive influence of seawater. Due to external load, the RC slab was partly cracked before the exposure to seawater. Consequently, the damaged part of the slab exhibits a much shorter depassivation time than the undamaged part. This is due to the cracking of concrete, which significantly accelerates processes that are relevant for depassivation of reinforcement. It is shown that depassivation in the cracked concrete is reached almost immediately after the attack of chlorides. The numerical results are in good agreement with the available experimental observations.
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